The Giro, along with the Tour de France and Vuelta a España comprise the world's three major tours and the Italian race's "Big Start" in Israel will mark the first time a cycling classic has included stages outside Europe.
The main focus during the race will be on Team Sky's four-time Tour de France winner Chris Froome, who has not competed at the Giro since 2010 but is aiming to be the first rider since 1983 to hold all three major tours concurrently.
However, the Briton is under investigation by the sport's governing UCI over an adverse doping test result after a urine sample showed excessive levels of an asthma medication at last year's Vuelta. Froome has denied any wrongdoing.
"I'm here to give my absolute best for the next three weeks, obviously, with the aim of trying to stand on that top step once we reach Rome," Froome said at the Team Sky pre-race news conference in Jerusalem.
Sylvan Adams, a Canadian-born Israeli entrepreneur and cycling enthusiast credited with bringing the Giro to Israel, has set up the Israel Cycling Academy team that will compete in the race. It includes two Israeli riders, another first.
"The Giro d'Italia is the largest sports event ever to be held in Israel," Sports Minister Miri Regev said, "this is a huge production and an unprecedented logistical operation."
The 101st Giro opens with a 9.7 km individual time trial on Friday in Jerusalem followed by road races on the next two days between Haifa and Tel Aviv (167km) and then Beersheba and Eilat (229km).The event has also attracted state funding aimed at boosting tourism by exposing the country to about a billion TV viewers. Tourism Ministry Director-General Amir Halevi said it was hoped that an investment of several million euros would yield a much larger return.
As part of a cycling drive, Adams has also backed the building of a new velodrome in Tel Aviv, which was unveiled on Tuesday. He said he hoped Israel would copy the British model and make it a cycling power.
"We are hoping to take a page out of British cycling, who became the world's pre-eminent cycling power after they built their velodrome in Manchester and the National Cycling Centre... so we are hoping to develop cycling amongst the youth and reach the highest level of the sport," Adams said.
Yoni Yarom, the head of Israel's cycling federation, said there were some 2,200 competitive riders among a population of nine million and a cycling culture has developed over the years, with more than 165,000 enthusiasts at all levels.
This year's race has been dedicated to the memory of Gino Bartali, one of Italy's great cyclists who won the Giro in 1936, '37 and '46, and the Tour de France in 1938 and 1948. He was honoured by the Yad Vashem Holocaust memorial on Wednesday.
During World War Two, Bartali, who died in 2000, deceived soldiers who assumed he was training, and helped save Jews from deportation to death camps by smuggling counterfeit identity documents past Fascist and Nazi checkpoints.